Is CCDC157 p.Arg121Gln (c.362G>A) pathogenic?

CCDC157 p.Arg121Gln (c.362G>A) is classified Uncertain significance in CCDC157 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.0975); Very rare (popmax 0.00269%, afr).

How common is CCDC157 p.Arg121Gln (c.362G>A) in the general population?

CCDC157 p.Arg121Gln (c.362G>A) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about CCDC157 p.Arg121Gln (c.362G>A)?

AlphaMissense predicts likely benign (score 0.0975) — an in-silico prediction, not a clinical call.

CCDC157 p.Arg121Gln

c.362G>A · VCV3486166

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0975 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0975	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP 0.65
Regional constraint	o/e 0.96	unconstrained · MANE · 11 kb · p 0.19 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,294 alleles

Filtering AF 0.000617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000476%

Overall 0.000998% 16/1,603,408 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,147
South Asian	0.00111%	90,194
European (non-Finnish)	0.00111%	90,395

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CCDC157
Protein: p.Arg121Gln
Coding: c.362G>A
MANE Select: NM_001017437
Type: single nucleotide variant
Location: chr22:30369545 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.73

Full CCDC157 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC157 p.Arg121Trp Uncertain significance ★ ⚠ same residue
CCDC157 p.Arg45Leu Uncertain significance ★★ ⚠ same type
CCDC157 p.Ala223Pro Uncertain significance ★ ⚠ same type
CCDC157 p.Ala292Val Uncertain significance ★ ⚠ same type
CCDC157 p.Ala300Thr Uncertain significance ★ ⚠ same type
CCDC157 p.Ala317Thr Uncertain significance ★ ⚠ same type
CCDC157 p.Ala324Ser Uncertain significance ★ ⚠ same type
CCDC157 p.Ala32Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ccdc157-p-arg121gln (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown